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Hepatic Immune Response to Environmental Carcinogens
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research. Univ Sulaimani, Dept Microbiol Immunol, Coll Med, Sulaimani, Iraq.
Univ Sulaimani, Dept Med, Coll Med, Sulaimani, Iraq.
Minist Higher Educ & Sci Res, Erbil, Iraq.
Univ Sulaimani, Coll Vet Med, Sulaimani, Iraq.
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2018 (English)In: Pharmacognosy Magazine, ISSN 0973-1296, E-ISSN 0976-4062, Vol. 14, no 58, p. 548-553Article in journal (Refereed) Published
Abstract [en]

Aim: Environmental carcinogenic substances contribute to increasing incidence of hepatocellular carcinoma (HCC). We employed a sensitive method for the detection of DNA damage combined with analysis of the immune response to gain better knowledge how environmental carcinogens mediate pathology.

Materials and Methods: Rat hepatocytes were isolated and stimulated with carcinogenic substances for the assessment of DNA damage. The mycotoxin aflatoxin B-1 (AFB(1)), two heterocyclic amines from the cooking of meat amino-3-methylimidazo[4,5-f] quinoline (IQ) and 3-amino-1-methyl-5H-pyr ido-(4,3-b)-indole (TRP-P-2), and protein extract from the fungus Lactarius necator were assayed. Unscheduled DNA synthesis in hepatocytes was measured by the incorporation of radioactive thymidine during DNA repair. Stimulation of hepatocyte/immune cell preparation with the substances and measurement of IFN gamma release at different time points determined their ability to induce an inflammatory response.

Results: DNA repair in the hepatocytes was induced in response to 10(-7) M AFB(1) and 10(-9) M IQ. TRP-P-2 did not induce DNA repair; however, at 10(-4) M, the fungus extract did this. Furthermore, liver-resident immune cells responded with differential production of IFN gamma over time in response to stimulation by all the carcinogens, with AFB(1) being the most potent. TRP-P-2 showed the most significant reduction in IFN gamma response over time.

Conclusion: DNA damage in hepatocytes induced by environmental substances was detected at low molecular concentrations. The system did provide novel evidence for hepatic carcinogenicity by the fungus L. necator. Analysis of the response by liver-resident immune cells to the substances suggested that highly mutagenic substances induce prolonged inflammatory response.

Place, publisher, year, edition, pages
2018. Vol. 14, no 58, p. 548-553
Keywords [en]
DNA damage, hepatocytes, immune response, inflammatory response, mutagenic substances
National Category
Cell Biology
Identifiers
URN: urn:nbn:se:uu:diva-371408DOI: 10.4103/pm.pm_242_18ISI: 000451220800014OAI: oai:DiVA.org:uu-371408DiVA, id: diva2:1273433
Available from: 2018-12-21 Created: 2018-12-21 Last updated: 2018-12-21Bibliographically approved

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